Our mathemafical/computafional Preliminary Studies emphasize the analysis of experimental data collected by our mulfidisciplinary team at Center of Cancer Systems Biology in conjuncfion with human data from the literature, to construct a predicfive model of dynamic steps in carcinogenesis Initiation consists of one or more comparatively rapid genomic or epigenetic alterations; the alterations produce cell clones that may become dysplasfic or hyperplastic and are at risk for being transformed. Promotion, according to one common view, involves the proliferation of initiated, and thus premalignant, cells. Promofion may take many years and the cell lineages may incur addifional alterations. (Malignant) transformation is a further genomic or epigenefic alterafion in an inifiated/promoted lineage. Somefimes, transformation is considered to be one point mutafion in a key gene, but other models consider larger scale DNA changes (e.g. deletions, duplicafions, translocafions and inversions, aneuploidy, or horizontal transfer) and/or consider mulfiple alterafions instead of just one alterafion. Progression occurs as a malignant cell lineage evolves in interacfion with its microenvironment, often becoming increasingly malignant and invasive. Genomic instability is a common feature. Many computational models implement all or part of this fimeline, often with addifional steps (reviewed, e.g., in [Cox & Huber 2007; Little et al. 2008a]). One basic implementafion is the classic two-stage clonal expansion (TSCE) model [Moolgavkar & Luebeck 2003], which emphasizes probabilisfic promotion. Two-stage refers to initiation to pre-malignancy (stage 1) and transformation to malignancy (stage 2).